Denis Krndija

Congrats, Adrien! 👏

Group Leader Call at the @cbitoulouse.bsky.social in
Genome biology, projects at the interface with devbio will be given particular attention. please share :)
cbi-toulouse.fr/wp-content/u...

Development builds... But it also breaks!

Planarians split to reproduce. Hydra tears open a mouth. Embryos fracture to make cavities.

Failure? No. Fracture is essential to development.

Our new review on fracture physics and its uses in development:

journals.biologists.com/dev/article/...

Excited to share our work on epithelial multilayering - identifying why stem cell stay in the basal layer and how and why differentiating cells move up. Great collab with @manningresearch.bsky.social and Niessen labs! Check out preprint and great summary below www.biorxiv.org/content/10.6...

Cytoplasmic crowding acts as a porous medium reducing macromolecule diffusion | PNAS Intracellular transport of macromolecules is crucial for the proper functioning of most cellular processes. Although intracellular crowding is know...

Happy to highlight our collaborative work from our @ijmonod.bsky.social team with @destriano.bsky.social, B. Goyeau and M. Chabanon.
Cytoplasmic crowding acts as a porous medium that hinders macromolecular diffusivity.
Plus: a clever way to measure cell volume.
www.pnas.org/doi/10.1073/...

Paper alert! β-catenin forms condensates that help build cell–cell adhesions - showing its role goes beyond simply linking E-cadherin to α-cat/actin. Great collaboration with the Schuijers lab!

👉 nature.com/articles/s41...

New paper out!
We show how mechanosensitive adherens junction proteins link actomyosin contractility to actin assembly using in vitro reconstitution.
Huge congrats to Aurélie Favarin, Rayan Said, & all authors!
In Science Advances: www.science.org/doi/10.1126/...
#actin #myosin #mechanobiology

#HappyNewYear !
Let's start 2026 with a @cellcommlab.bsky.social paper

How many branches is OK during #CellMigration?
It depends on the #cell: for ex. immune cells are just fine.

In collab. w. #NirGov @hfspo.bsky.social

Full www.science.org/doi/10.1126/...
@focalplane.bsky.social @science.org 🧪🔬

Christmas lunch of team Krndija

Good times at our traditional Christmas team lunch today 🎄🥂
It was a year full of exciting results, marked by our first PhD student graduating and two preprints published!
Very grateful for this team and all that we’ve achieved together over the past four years.
Looking forward to what’s next! 🙏✨

🚨🚨🚨
The SFBD board needs to be renewed with 5 members
We wish to strengthen our board with young scientists

To apply: send a brief text introducing your research interests and motivations to sfbd@sfbd.fr by December 4th
Elections will be held online from December 10th to 17th
Please share the info

Mechanosensitive calcium channels and integrins coordinate the reprogramming of colorectal cancer cells into a fetal-like state van der Net et al. show that mechanical interactions with the stromal component collagen I trigger reprogramming of colorectal cancer cells into a fetal-like state, through mechanosensitive integrins ...

We finally made it over here ! And excited to share our new paper on mechanical forces regulating stem cell plasticity in colorectal cancer, involving force transduction via mechanosensitive calcium channels! www.cell.com/cell-reports...

Great opportunity - check it out!👇🤩

Thanks, Bertrand! We just thought it’s time to give faeces the mechanical respect it deserves! 💪💩

Delighted that Ziqi Dong's PhD paper is out for all to read! Hypoxia is fundamental to normal development, and fascinating! Thanks to all of our co-authors including @jamesnathanlab.bsky.social @jellevda.bsky.social authors.elsevier.com/sd/article/S...

📢Si vous êtes passionné.e par les cellules souches, la régénération tissulaire avec un intérêt pour les pathologies intestinales mais aussi la microfluidique, et vous voulez participer au programme national PEPR MED-OOC, cette offre de thèse est pour vous:
www.adum.fr/sujetT?id=67...

🔬 Postdoctoral Opportunity in Biomedical Research. #Organoids & #Organs-on-Chip for #IBD and #Personalized #Medicine at #i2mc in #Toulouse, #France at the crossroads of #stem cell biology, #microphysiological systems, and translational medicine.

👉 Apply before Nov. 1rst at audrey.ferrand@inserm.fr

How do cells navigate up gradients of adhesive proteins?
🤔

Termed "Haptotaxis", this effect is ubiquitous in cell migration, but it's mechanism was poorly understood

We show that passive friction directs cells & explains complex trajectories on gradients

👉 www.nature.com/articles/s41...

Amazing work by Vishnu & the MechanoGut team! 💩⚙️🛠️ Huge thanks to @cbitoulouse.bsky.social imaging & animal facilities, our dear colleagues and collaborators, and funders @cnrs.fr ATIP-Avenir, ED-BSB, @frm-officiel.bsky.social
#Mechanobiology #GutBarrier #EpithelialBiology #CellAdhesion

Pathologically, when this adaptive capacity is exceeded – as in IBD, fibrotic strictures, obstruction, or toxic megacolon – barrier failure and inflammation may ensue. Understanding these mechanisms could inform new strategies to restore epithelial integrity in disease.

Our findings resonate with work from A. Yap, A. Miller, K. Green, C. Niessen, G. Charras and others on how junctional tension and cytoskeletal coupling sustain epithelial resilience. We reveal that such mechano-adaptive coordination also operates in vivo, in an adult organ under mechanical stress.

Also, this work sheds more light on the unexpected dynamics of desmosomes and intermediate filaments – long seen as static anchors, now increasingly recognised as mechano-responsive players in epithelial resilience!

🧠 Take-home:
The gut epithelium isn’t a passive barrier – it’s relentlessly adaptive.
Extrinsic forces from faeces trigger a rapid, coordinated reinforcement of all junctional complexes, preserving barrier function and homeostasis under continuous stress 💩💪 (11/11)

Top: Schematic of the proposed mechanoadaptation pathway in colonic epithelium, illustrating how failed junctional recruitment may lead to barrier breach. Left: Representative images of colonic epithelium stained for F-actin (cyan) and acc. E-cad (grey) in NMMIIA-KO mice from ND and faeces-D regions. Red arrows indicate breached junctions. Maximum Z-projection (1-3 µm range). Scale bar: 5 µm. Right: Bar plots showing percentage of accessible E-cad (acc. E-cad)-positive junctions in control and NMMIIA-KO mice from ND and faeces-D regions, or in ND and D explants after indicated treatments.

Using a luminal-accessibility assay for E-cadherin, we found that depleting NMIIA in vivo or inhibiting myosin II / Ca²⁺ influx ex vivo led to barrier breaches under mechanical stress.
The junctional response is therefore essential for maintaining epithelial integrity (10/11)

Left: Representative images showing colonic explants, stained for ZO-1 (magenta) and pMLC (S19) (cyan) in ND after Yoda1 or vehicle control (DMSO) treatment for 15 min. Maximum Z-projection (1-3 µm range). Scale bar: 5 µm. Top-right: Box plot showing junctional pMLC intensity in Yoda1-treated and vehicle control (DMSO)-treated ND explants. Bottom-right: Comparative box plot showing junctional ZO-1 intensity fold change in distended explants after pre-treatment with mechanosensitive ion channel inhibitors or Piezo1 activator. Dotted line represents the normalised average for ND.

Conversely, activating Piezo1 was enough to trigger NMII activation and junctional recruitment.
👉 Mechanosensitive Ca²⁺ influx is both necessary and sufficient for junctional reinforcement under force ⚡️(9/11)

Left: Representative image showing colonic explants, stained for ZO-1 in ND and D after Gd3+ or vehicle control (water) treatment as indicated in (B). Maximum Z-projection (1-3 µm range). Scale bar: 5 µm). Right: Box plot showing junctional pMLC intensity in Gd3+ treated and vehicle control (water)-treated ND and D explants.

💡 What activates myosin II under mechanical stress?
Blocking mechanosensitive ion channels (with Gd³⁺) or chelating extracellular Ca²⁺ (with BAPTA) prevented NMII activation and junctional reinforcement – stopping the mechano-adaptive response in its tracks (8/11)

Left: Representative image of colonic epithelium stained for ZO-1 in control and NMMIIA-KO mice from ND and faeces-D regions. Maximum Z-projection (1-3 µm range). Scale bar: 5 µm. Top-right: Comparative box plot showing fold change in junctional protein levels (tight junctions (TJ), adherens junctions (AJ) and desmosomes (DS)) in faeces-D regions of controls and NMMIIA-KO mice. Dotted line represents the normalised average for ND. Bottom-right: Comparative box plot showing junctional ZO-1 intensity fold change in distended explants after pre-treatment with upstream myosin II inhibitors or Calyculin A. Dotted line represents the normalised average for ND.

Genetic deletion (Myh9-KO in vivo) or pharmacological inhibition of NMII ex vivo abolished junctional recruitment across all complexes.
👉 NMII acts as a central effector coordinating force sensing and junctional reinforcement.🔩 (7/11)

Left: Representative images, segmented and colour-coded based on apical cell area in ND and D regions after 5, 15 and 30 min of distension. Maximum Z-projections (1-3 µm range). Scale bar: 5 µm. Right: Line plot showing mean fold change in cell area and NMMIIA-GFP intensity after 5, 15 and 30 min of distension. Dotted line represents the normalised average for ND.

Junctional reinforcement coincided with recruitment of myosin IIA (NMIIA) to perijunctional belts and transient apical constriction – hallmarks of contractile activation.
Unexpectedly, myosin IIC, usually linked to microvilli, also relocalized to junctions under force ⚙️ (6/11)

Top: Scheme showing experimental approach for catheter-mediated in vivo distension of the mouse colon. Bottom-left: Comparative line plot showing junctional intensity fold change for ZO-1, E-cad and PG after 5, 15 and 30 min of distension. Dotted line represents the normalised average for ND. Bottom-right: Comparative line plot showing junctional intensity fold change for DP and KRT8 after 5, 15 and 30 min of distension. Dotted line represents the normalised average for ND.

Using a controlled in vivo colonic distension system (with Nicolas Cenac, IRSD Toulouse), we uncovered two kinetic modes:
- Tight & adherens junctions → sustained reinforcement
- Desmosomes & keratin filaments → progressive accumulation over time (5/11)

Left: Scheme showing adhesive cell-cell junctions in colonic epithelium. Middle: Representative en face images of colonic epithelium, stained for tight junction (TJ) protein ZO-1, Adherens junction (AJ) protein E-cad, and desmosomal (DS) protein Desmoplakin (DP) and desmosome-associated intermediate filament (IF), K8 in both ND and D regions. Maximum Z-projections (1-3 µm range). Scale bar: 5 µm. Right: Representative transverse images of colonic epithelium, stained for K8 (cyan) and DP (magenta) in both ND and D regions. Maximum Z-projections (2-4 µm range). Scale bar: 5 µm

This mucosal remodelling comes with striking reinforcement of tight, adherens, and desmosomal junctions – a robust, pan-junctional mechano-adaptive response.
The adult gut epithelium actively adapts to physiological mechanical stress 💪 (4/11)

Representative images of thick section of mouse colonic tissue in transverse view, showing lumen, plateau regions (white brackets), muscle layers and crypts (outlined in yellow dashed lines), and stained for F-actin (magenta), DAPI (cyan) and laminin (grey) in both ND and D regions. The left panel is a tiled confocal reconstruction. Right panel: Representative transverse images of plateau regions in the colonic epithelium, stained for F-actin (magenta), DAPI (cyan) and laminin (grey) in both ND and D region. Basal side of the cell outlined as yellow dashed line. Maximum Z-projections (2-4 µm range). Scale bars: left panel, 500 µm; middle panel, 50 µm; right panel: 5 µm.

💩 Faeces matter – mechanically!
Most studies remove luminal contents before analysis – we didn’t.
Keeping them revealed that the colonic mucosa adapts to faecal distension through large-scale tissue unfolding and epithelial deformation (3/11)